Tricyclic antidepressants, thyroid function, and their relationship with the behavioral responses in rats.
We first studied the effects of tricyclic antidepressants (TCAs) on thyroid function in rats in the learned helplessness paradigm. TCAs (clomipramine 32 mg/kg, desipramine 16, 24 mg/kg, or imipramine 8, 16, 32 mg/kg per day) were injected IP for 5 consecutive days. Blood samples were collected 1 hr after the last administration of the antidepressant for radioimmunoassay determination of triiodothyronine (T3) and thyrotropin. Whereas inducing helplessness did not result in any change in T3 and thyroid-stimulating hormone (TSH) levels, TCA therapy dose dependently decreased the T3 levels without changing TSH levels in helpless animals and in naive control rats. To further the investigation, the effects of TCAs on thyroid function were examined using two models of experimentation, one involving diabetes induction, the other using food deprivation; both are known to induce a resistance to TCAs that is reversible under T3 treatment. In both models, a decreased T3 level existed prior to the TCA administration. Although they had no effect on behavior, TCAs further decreased the T3 levels in diabetic and food-restricted rats. This study confirms that TCAs decrease thyroid function and suggests that the antidepressant effect of TCAs is not related to their T3 decreasing effects.
Massol
J
J
Département de Pharmacologie, Faculté de Médicine, Pitié-Salpêtrière, Paris, France.
Martin
P
P
Chatelain
F
F
Puech
A J
AJ
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001143:Arousal / Q000187:drug effects*; D001362:Avoidance Learning / Q000187:drug effects; D002997:Clomipramine / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000523:psychology; D004924:Escape Reaction / Q000187:drug effects; D006380:Helplessness, Learned; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013960:Thyroid Function Tests; D013963:Thyroid Hormones / Q000097:blood*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D014285:Triiodothyronine, Reverse / Q000097:blood
D000929:Antidepressive Agents, Tricyclic; D013963:Thyroid Hormones; D014284:Triiodothyronine; D014285:Triiodothyronine, Reverse; D013972:Thyrotropin; D002997:Clomipramine; D007099:Imipramine; D013974:Thyroxine; D003891:Desipramine